Since the invention of G0069A (JP 61-212587) and Tu 1718 (DE 3727651), we paid attention to develop .beta.-lactam class of compounds as antitumor agents. However, there were a lot of difficulties to obtain these compounds in large scales. For example, only 20 mg of G0069A was isolated from 10 L fermentation broth even after under well controlled fermentation techniques and suitable experimental conditions. On the other hand, another .beta.-lactam compound having the same stereochemistry at C.sub.5, (3R,5S)-3-hydroxymethyl-4-oxa-1-azabicyclo[3.2.0]heptan-7-one (clavam 1, G0069B) was isolated by Brown and Evans (J. Chem. Soc. Chem. Comm. 1979, 282) from the culture of Streptomyces clavuligerus, which is reported to exhibit antifungal activity. We have synthesized clavam 1 and have done extensive biological evaluation. We found that clavam 1 exhibit excellent antitumor activity both in vitro and in vivo but is chemically unstable. ##STR2##
The chemical unstability may be due to the intermolecular interaction of --OH to the .beta.-lactam ring which results in the decomposition of product.
As a part of the program directed toward the development of .beta.-lactam class of compounds as novel antitumor agents, it is necessary to get compounds which are relatively easy to synthesize, chemically stable and have strong antitumor activity.